Safety and efficacy of nitric oxide in chronic lung disease.

BACKGROUND: Therapies for neonatal chronic lung disease (CLD) of prematurity have had limited success. AIMS: To determine whether inhaled nitric oxide (INO) administered to very low birthweight infants with developing CLD might improve oxygenation without adverse effects. METHODS: Subjects were 10-30 days of age, birth weight < 1250 g, with developing or established CLD, and requiring mechanical ventilation with mean airway pressure > or = 7 cm H2O and FIO2 . or = 0.40. We monitored changes in oxygenation and FIO2 requirement during treatment with INO (initial dose 20 ppm). Tracheal aspirate samples obtained before, during, and after treatment were analysed for interleukin 1beta (IL-1beta), IL-8, 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), laminin, and endothelin 1 (ET-1) to assess any potential effects of INO on markers of inflammation peroxidation, basement membrane injury, or vasoactivity. RESULTS: Thirty three patients met entry criteria. Mean gestational age was 25 (SD 2) weeks; birth weight was 736 (190 g); age of study infants was 19 (6) days (range 9-29). Mean FIO2 decreased from baseline (0.75) to 0.58 at 72 hours. Duration of therapy was seven days. Tracheal aspirate concentrations of IL-1beta, IL-8, 8-epi-PGF2alpha, ET-1, and laminin were unchanged between baseline and 48 hours of INO, and 48 hours after discontinuation of INO. No new cases of, nor extension of, intraventricular haemorrhage occurred. Four infants died. CONCLUSION: INO (< or = 20 ppm) improved oxygenation in most infants with early CLD, without inducing changes in markers of inflammatory or oxidative injury.

Markers of chronic infection and inflammation. Are they important in cases with chronic coronary heart disease.

The human cytomegalovirus plays a causal role in atherosclerosis etiology, but it is discussed as controversial. We conducted a case control study to investigate whether previous infection with cytomegalovirus is associated with coronary heart disease and markers of systemic inflammation, because systemic inflammation may play a role in atherosclerosis too. We also studied the correlation between anti-cytomegalovirus antibody titer and coronary artery disease. The study involved 150 cases (45 females, mean age +/- SD is 58.73 +/- 7.68 years) with a documented coronary heart disease and 160 healthy volunteers (50 females, mean age +/- SD is 57.82 +/- 7.68, p > 0.05). Cytomegalovirus serology was performed to determine the presence of specific IgG antibodies and titers of the anti-cytomegalovirus IgG antibodies. In addition, C-Reactive protein levels were determined for each case. The prevalence of specific antibodies to cytomegalovirus was 57.30% for the patients and 56% for the controls (p = 0.39). But higher levels of anti-cytomegalovirus IgG antibody titer (> 1/800) were seen in the patient group (28.6% versus 10%, p = 0.0000). Mean value of C-reactive protein was higher in the patient group (2.99 +/- 0.92 mg/l versus 1.79 +/- 0.51 mg/l, p = 0.0000), and there was a linar correlation with the high antibody titers and the level of C-reactive protein (r = 0.35, p = 0.0000) These findings support that not the seropositivity of the population but rather the titer of anti-cytomegalovirus antibody and the levels of C-reactive protein could predict patients with a high risk of coronary heart disease.

Two cases suggesting a role for the L-arginine nitric oxide pathway in neonatal blood pressure regulation.

Endogenous nitric oxide produced from L-arginine is a potent vasodilator that may be involved in blood pressure regulation. A male infant with argininosuccinate lyase deficiency, who could not synthesize L-arginine, was hypertensive prior to L-arginine replacement. The infusion of L-arginine resulted in a decrease in blood pressure. A three-fold increase in the dose of L-arginine further decreased blood pressure. On discontinuing the infusion of L-arginine, the patient's blood pressure increased. A female infant undergoing an L-arginine challenge test had a decrease in blood pressure during L-arginine infusion which resolved when the L-arginine infusion was discontinued. These two cases suggest that nitric oxide production from L-arginine may play a role in the normal regulation of systemic blood pressure.